As a result of extensive investigation performed over the past several decades, various metabolites and analogs of vitamin D have been isolated and prepared. For example, metabolites, such as 25-hydroxycholecalciferol and 1.alpha.,25-dihydroxycholecalciferol, have been isolated from liver and kidney homogenates, respectively, and analogs, such as 1.alpha.-hydroxycholecalciferol, have been prepared from natural sources. Vitamin D and its known metabolites and analogs stimulate intestinal calcium transport and mobilize bone calcium with varying degrees of efficacy depending upon the degree and position of hydroxylation of the vitamin D molecule, but with virtually no separation of activity. Vitamin D and its known metabolites and analogs are potent intestinal calcium transport stimulators and potent bone calcium mobilizers.
Also as a result of these investigations, it has been established that vitamin D and its metabolites are hydroxylated at the 1.alpha.-position by the kidney and that 1.alpha.-hydroxylation is essential for biological activity in anepheric animals and man.
This subject is thoroughly reviewed by DeLuca, et al. in Physiological Reviews, 53, 327 (1973).
Potent vitamin D analogs selectively stimulating intestinal calcium transport without significantly mobilizing bone calcium would be highly desirable additions to the physicians's arsenal of drugs for the treatment of certain vitamin D metabolic disorders, such as osteoporosis. For the treatment of a wide spectrum of vitamin D related diseases associated with kidney failure or chronic uremia, potent vitamin D analogs bearing the key 1.alpha.-hydroxyl group eliminating the necessity for renal metabolism would also be highly desirable additions.